Automated device for a biologic drug distribution

ABSTRACT

The present disclosure relates to an apparatus for dispensing biologic drug compositions. The apparatus includes an automated device that can store a biologic drug under the desired conditions. When authorized, the automated device can process the stored biologic drug by performing the desired processing steps to prepare the biologic drug for administration to a patient. The automated device may include a computing system to transmit patient information to a remote location and receive authorization from a remote location.

CROSS-REFERENCE TO RELATED APPLICATION

This Application is a Continuation of International Application No.PCT/US2012/055142, filed Sep. 13, 2012, in English, U.S. provisionalapplication Ser. No. 61/534,642, filed Sep. 14, 2011, U.S. provisionalapplication Ser. No. 61/561,101, filed Nov. 17, 2011, U.S. provisionalapplication Ser. No. 61/620,651, filed Apr. 5, 2012, and U.S.provisional application Ser. No. 61/667,633, filed Jul. 3, 2012, thecontents of which are hereby incorporated by reference in theirentirety.

FIELD

This disclosure relates to automated devices and more particularlyautomated devices for use in distribution of biologic drugs.

BACKGROUND

Automated devices such as vending machines have been used for dry goods,refrigerated foods and/or frozen foods for a long time. The vendingmachines are placed in locations convenient to the consumer. When theconsumer desires the product, he or she physically deposits cash or acredit card into the machine, makes a selection and receives theproduct.

More recently, automated devices have been used for conveying regulatedpharmaceuticals. In acquiring regulated pharmaceuticals, a consumer inaddition to providing payment must also provide documentation in somemanner that they are eligible and permitted to receive the product. Inthis case also, the consumer physically interacts with the automateddevice to provide payment and permission for obtaining the product.These pharmaceuticals generally include dry or liquid pharmaceuticalsand are regulated in order to prevent fraud and/or abuse.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a flow chart illustrating steps in a method of distribution ofthe living cell biologic drug.

FIG. 2 is a schematic drawing of some of the main components of oneembodiment of a vending machine of the present invention.

SUMMARY

In a first aspect, the invention relates to an automated devicecomprising a storage chamber for storing a biologic sample, a processingcompartment, a system for receiving authorization to transfer thebiologic sample from the storage chamber to the processing compartmentand a dispensing chamber for receiving the biologic sample afterprocessing. The system for receiving authorization in the device caninclude a computer with an internet connection.

In another aspect, the invention relates to a method for dispensing adose of biologic drug. The method includes storing the biologic drug inan automated device under desired conditions, and processing thebiologic drug in the automated device upon receipt of authorization toprocess a dose of the biologic drug. The method can also include a stepwherein the biologic drug is manufactured at a remote location, storedfor long-term storage and transported for placement in the automateddevice.

In yet another aspect, the invention relates to a method for providing abiologic drug. The method includes manufacturing the biologic drug in amanufacturing facility, transporting the biologic drug to a point ofcare site wherein the biologic drug is transported under conditions tomaintain the biologic activity of the drug and storing the biologic drugin an automated device at the point of care site until a patient isauthorized for receiving the biologic drug.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

The present description relates to an automated device or vendingmachine for live biological drugs. The biologic drugs include livingcells that are maintained in a frozen state in the vending machines. Thevending machines are generally placed in a point-of-care site, forexample, a clinic, a hospital or other healthcare setting. The vendingmachine may also include a connection to a remote location generallythrough a secure internet connection. The connection can be used totransmit patient information such as medical records and detailsregarding financial payment. The remote location can be anywhere in theworld and can be staffed by people that can verify the patient recordsand collect payment for the biologic drugs or obtain sufficientinformation regarding commitment for payment. Once the patient isapproved for receiving the biologic drug, the patient, doctor or otherhealthcare worker can interact with the machine directly or through theuse of a computer and start the processing cycle. Alternatively, theautomated device may receive a code directly from the remote sitethrough an internet connection to start the processing of a sample ofthe biologic drug.

The processing cycle can include, for example, retrieving a dose of theliving cell drug, thawing, washing, incubating and formulating thesample for administration to the patient. The processing cycle can havea variable time duration and can be as little as several minutes or aslong as a day. In exemplary embodiments, the processing cycle may takeseveral hours. The actual events and components involved in theprocessing cycle can vary and depend on the specific biologic drugdispensed and formulated for administration to a patient. Uponcompletion of the processing cycle by the vending machine, the biologicdrug can be retrieved by a person such as a health care worker andadministered to the patient. Health care workers can include a doctor,nurse, technician and the like. A patient or a layperson trained inhandling the biologic drug may also retrieve the biologic drug from theautomated device.

Storage and processing of the biologic drug in an automated device asdescribed herein advantageously alleviates the patient's need to travelto a site where the biologic drug is manufactured. In other words, themethod employed herein for storing and processing the biologic drugenables the drug to be manufactured anywhere in the world and be used bya patient at a point of care site anywhere in the world. In addition,since the processing of the sample is performed in an automated devicethere is less chance of the sample being mishandled by a worker.

The present description also includes a novel business method. Thismethod includes preparing a frozen biologic drug in a manufacturingfacility and distributing the frozen drug to point-of-care sites. Thefrozen biologic drug is stored in an automated device capable ofmaintaining the drug in a frozen state at a point of care site untilneeded by a patient. When a doctor prescribes the use of the biologicdrug to a patient, the patient's medical information and financialpayment information is transmitted over a secure link to a remotelocation for authorization. Upon authorization, the automated device canbe activated to initiate a processing cycle to prepare the drug foradministration. The doctor or other authorized healthcare worker canobtain the drug after completion of the processing cycle and administerit to the patient. Alternatively, the patient may retrieve theformulated drug from the dispensing chamber and self-administer thedrug.

The biologic drugs placed in the automated devices include living cellsthat have been manipulated in a number of ways. These manipulationsinclude cells that have been proliferated, differentiated, activated andthe like. In some embodiments, these living cells are immune cells andother embodiments, the living cells are activated T-cells. These immunecells may have been activated as described, for example, in U.S. Pat.Nos. 7,435,592, 7,678,572 and 7,402,431 incorporated herein byreference. Living cells as described herein include cells that can befrozen, thawed and when placed in appropriate media can be viable livingcells that carry out cellular functions. The cellular functions caninclude secretion of molecules, proliferation, differentiation and thelike. The cellular functions can be carried out in vitro and/or in vivo.For purposes of this application the term cell(s) can includeprokaryotic and eukaryotic cells. In some preferred embodiments, thecells are eukaryotic cells. The biologic drug generally includes humancells but cells from other animals can be amenable to frozen living cellstorage.

The living cells after being manipulated in the desired manner forobtaining a biologic drug can be prepared for long-term storage byfreezing in the appropriate manner. The long-term storage can includesuspension of the cells in media suitable for maintaining the viabilityof the cells during freezing and upon thawing.

In one exemplary embodiment, the method of distributing a biologic drugis as shown in the flow chart of FIG. 1. In this method, the living cellbiologic drug is prepared in a manufacturing facility meeting theappropriate standards (step 10). After manufacturing of a batch of thebiologic drug, the biologic drug is divided into individual doses andplaced into vials or other suitable containers (step 20). The containerswith the individual doses are frozen for long-term storage (step 30),preferably at about −70° C. Some desired number of doses can be shippedto point-of-care facilities around the world (step 40). The shippingmethod used can maintain the cells at the desired temperature, i.e.about −70° C. The point-of-care facility, upon receiving the shipment offrozen biologic drug samples, stocks an automated device (a vendingmachine) already present at the site (step 50). The biologic drug isstored in the storage chamber of the vending machine at the desiredtemperature until needed by a patient.

In step 60, a patient, examined by a doctor, is identified to benefitfrom the biologic drug in the vending machine. Patient information istransmitted (step 70) to a remote location. The patient information caninclude, for example, patient's medical records, patient's financial,payment and/or insurance information. Other information regarding thepatient deemed necessary or useful may also be transmitted to the remotelocation. The patient information may be transmitted through a secureinternet connection within the automated device or connected to theautomated device. Alternatively, the patient information may betransmitted by a worker in the point of care facility through any othercomputing system with an internet connection or using other methods ofinformation transfer, preferably in a secure manner.

In step 80, a person at a remote location receives the patientinformation and determines if the patient will be authorized to receivea dose of the biologic drug in the vending machine. Authorizationdetermination can be made based on the patient medical condition,payment from the patient, and/or commitment of payment from the patient.Once the patient is approved for receiving the biologic drug, thepoint-of-care facility is notified and given permission to start theprocessing cycle of the frozen biologic drug (step 90). Thepoint-of-care facility, for example, may be given a code that must beentered into the vending machine for the processing cycle to begin. Uponentering the code, one dose of the biologic drug is moved from thestorage chamber to the processing compartment(s) (step 90). After theprocessing, the formulated drug is dispensed from the vending machine(step 100), removed and administered to the patient (step 110).

In an exemplary embodiment as shown in FIG. 2, vending machine (200)includes storage chamber 210 holding multiple doses of vials 220containing the frozen biologic drug described herein. Storage chamber210 is within cooling unit 230. Cooling unit 230 can include a varietyof cooling processes, and preferably maintains the biologic drug invials 220 at the desired temperature, for example, about −70° C. Vendingmachine 200 also includes power cord 214 that connects to a powersource. Vending machine 200 includes system 300 capable of having asecure internet connection. System 300 can be, for example, a computingsystem with a secure internet connection. The internet connection iscapable of communicating with computer 340 at a remote location. Theremote location can be, for example, in the next room, across thecountry or across the world. System 300 is capable of accessing patientinformation about a specific patient and transmitting the information tocomputer 340 at remote location. System 300 may be configured to accesspatient information in a variety of ways including from removable datastorage components such as a flash drive or zip drive or from accessinga network or a computer at the point-of-care site that has the patientinformation. System 300 may include, for example, keypad 310, displayscreen 320 and start button 330. A worker at the remote location canreview the patient information and if satisfactory, can approve thepatient for receiving a dose of biologic drug in vial 220. Once thepatient is approved, computer 340 at a remote location can transmitauthorization. Authorization can be verbal to a health worker from aworker at the remote location. Verbal authorization can simply instructthe health worker to press start button 330 to initiate the processingcycle. Alternatively, the health worker may be given a code to enterinto keypad 310 to initiate the processing cycle. Display screen 320 maydisplay the status of vending machine 200, for example, it may display“processing sample”, “washing sample” , etc. Alternatively,authorization can be by means of transmittal of a processing cycleinitiation code directly to system 300 of vending machine 200 fromcomputer 340.

In vending machine 200, upon receiving a start or initiation signal,vial 220 is moved to thawing chamber 240 in processing compartment 236.In thawing chamber 240, vial 220 is thawed to form thawed sample 220 a.Thawing chamber 240 has the appropriate components and/or materialsnecessary for thawing a biological sample. Chambers 250, 260, and 270can be washing, incubating and formulating chambers, respectively.Chambers 250, 260 and 270 also have the appropriate components and/ormaterials necessary for carrying out their respective processing steps.The samples in vials 220 b, 220 c and 220 d are washed sample, incubatedsample and formulated sample, respectively. Once the sample isformulated, it is moved to dispensing chamber 280. Vial 220 e indispensing chamber 280 can be removed and is ready for administration tothe patient. Generally, the formulated sample is administered to thepatient immediately or as quickly as possible. Preferably, the sample isadministered to the patient within 4 hours of formulation. The biologicactivity of the sample can decrease with time after the formulation ofthe sample.

Chambers 240, 250, 260 and 270 can be any type of chambers, i.e.thawing, washing, mixing, and can be specific to the specificrequirements of the biologic drug stored in vending machine 200.Embodiments are also contemplated wherein vending machine 200 includesonly one chamber for all of the processing and the different steps inthe processing are conducted while the sample is in the one chamber.

A variety of biologic drugs can be manufactured, stored and dispensedusing the devices and methods described herein. In an exemplaryembodiment, the manufacturing of a biologic drug at a remote facilityincludes obtaining T-cells from a healthy donor and differentiatingthese T-cells ex vivo. The ex vivo preparation of cells can includeengagement of the CD3 and CD28 cell surface proteins throughcross-linking, for example, by anti-CD3 and anti-CD28 antibodies asdescribed in, for example, U.S. Pat. No. 7,435,592. The ex vivo preparedcells can be frozen prior to transporting to a point of care facility.

At the point of care facility, the frozen ex vivo prepared T-cells canbe stored in an automated device and processed or formulated foradministration upon receipt of authorization or approval of a patientfor the biologic drug. The processing includes thawing the biologic drugand reactivating just prior to administration to a patient. Thereactivation of the cells can be as described in U.S. Pat. No.7,402,431. Briefly, the frozen cells can be thawed and reactivated byengaging cell surface proteins CD3 and CD28. The reactivation caninclude cross-linking the CD3 and CD28 proteins with, for example,anti-CD3 and anti-CD28 monoclonal antibodies. In some embodiments, theanti-CD3 and anti-CD28 monoclonal antibodies are attached tobiodegradable particles. These reactivated allogeneic T-cells produceinterferon-gamma and express high density CD40L on the cell surface.

The biologic drug stored and processed in automated devices describedherein exhibit a substantial amount of biological activity. The amountof biological activity exhibited can vary and depend on the length ofstorage, the conditions of transport and storage, the specific biologicactivity and the nature of the living cells. Preferably, the biologicdrugs described herein, upon formulation, exhibit at least about 50% ofthe biologic activity relative to the activity of the biologic drugformulated at a manufacturing facility. More preferably, the biologicdrugs exhibit at least about 80 percent of the activity, and even morepreferably, at least about 95 percent of the activity after processingcompared to a biologic processed at the manufacturing facility.

Although the present invention has been described with reference topreferred embodiments, workers skilled in the art will recognize thatchanges may be made in form and detail without departing from the spiritand scope of the invention.

1. An automated device comprising: a storage chamber for storing abiologic drug; a processing compartment; a system for receivingauthorization to transfer the biologic drug from the storage chamber tothe processing compartment; and a dispensing chamber for receiving thebiologic drug after processing.
 2. The device of claim 1 wherein thestorage chamber comprises a freezer for maintaining the biologic drug ata desired temperature.
 3. The device of claim 2 wherein the freezermaintains the biologic drug at about −70° C.
 4. The device of claim 1wherein the processing compartment comprises apparatus and materials forprocessing the biologic drug for administration to a patient.
 5. Thedevice of claim 4 wherein the processing comprises thawing, washing,mixing, crosslinking, incubating, formulating and combinations thereof.5. The device of claim 4 wherein the processing compartment comprisesthawing apparatus and materials, washing apparatus and materials, mixingapparatus and materials, crosslinking apparatus and materials,incubation apparatus and materials, formulating apparatus and materialsand combinations thereof.
 7. The device of claim 1 wherein the systemfurther comprises an internet connection for transmitting patientinformation to a computer at a remote location.
 8. The device of claim 1wherein the system receives authorization through the internetconnection.
 9. The device of claim 1 wherein the authorization is byentry of a code.
 10. The device of claim 9 wherein the code is enteredin a computer at a remote location.
 11. The device of claim 1 whereinthe code is entered through a keypad on the device.
 12. The device ofclaim 1 wherein the storage chamber holds multiple doses of the biologicdrug.
 13. The device of claim 1 wherein the biologic drug comprisesliving cells.
 14. The device of claim 1 wherein the biologic drugcomprises immune cells.
 15. The device of claim 1 wherein the biologicdrug comprises activated T-cells.
 16. The device of claim 1 wherein thedevice is located at a point of care site.
 17. A method for dispensing abiologic drug comprising: storing the biologic drug in an automateddevice under desired conditions; and processing the biologic drug in theautomated device upon receipt of authorization to process drug.
 18. Themethod of claim 17 wherein the biologic drug is manufactured at a remotelocation, stored for long term storage and transported for placement inthe automated device.
 19. The method of claim 17 wherein the biologicdrug is stored at about −70° C.
 20. The method of claim 17 whereinauthorization comprises approval of a patient for receiving the biologicdrug.
 21. The method of claim 17 wherein the authorization stepcomprises receiving authorization from a remote computer through aninternet connection in the automated device.
 22. The method of claim 17wherein the processing comprises thawing, washing, mixing, crosslinking,incubating, formulating and combinations thereof.
 23. The method ofclaim 17 wherein the biologic drug regains biological activity after theprocessing.
 24. The method of claim 17 wherein the biologic drugcomprises living cells.
 25. The method of claim 17 wherein the biologicdrug comprises immune cells.
 26. The method of claim 17 wherein thebiologic drug comprises activated T-cells.
 27. The method of claim 17wherein the biologic drug comprises activated T-cells and processingcomprises reactivation of the T-cells prior to administration to apatient.
 28. A method for providing a biologic drug comprising:manufacturing the biologic drug in a manufacturing facility;transporting the biologic drug to a point of care site wherein thebiologic drug is transported under conditions to maintain the biologicactivity of the drug; and storing the biologic drug in an automateddevice at the point of care site until a patient is authorized forreceiving the biologic drug.
 29. The method of claim 28 wherein themethod further comprises processing the biologic drug in the automateddevice for administration to a patient.
 30. The method of claim 28wherein the biologic drug is frozen after manufacturing and remainsfrozen during transportation to the point of care site.
 31. The methodof claim 28 wherein the biologic drug comprises living cells.
 32. Themethod of claim 28 wherein the automated device comprises a computingsystem with an internet connection to transfer patient data and receiveauthorization to process the biologic drug for administration.